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Paper IPM / Cognitive / 11297 |
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In the present study, the effects of intra-dorsal hippocampus (intra-CA1) injection of cannabinoid receptor agents on memory formation have been investigated in 3-days apomorphine-treated rats. Stepthrough inhibitory avoidance task of memory has been used to examine retrieval of memory formation, 24 h after training. Apomorphine was injected subcutaneously (S.C.), once daily for 3-days followed by 5 days free of the apomorphine before training. Bilateral post-training intra-CA1 infusions of the non selective CB1?CB2 receptor agonist, WIN55, 212?2 (0.1, 0.25 and 0.5 ug/rat), dose-dependently shortened the step-through latency, suggesting amnesia by the drug, whereas bilateral post-training intra-CA1 micro-injections of the selective CB1 receptor antagonist, AM251 (25, 50 and 100 ug/rat), did not affect memory formation. Intra-CA1 infusions of AM251 and WIN55, 212?2, two min apart, modify the WIN55,212?2-induced reduction of step-through latency. Furthermore, the deleterious effect of WIN55, 212?2 (0.25 ug/rat) was completely abolished in rats previously given apomorphine (0.5 and 1 mg/kg/day, S.C.) for 3 days. This prevention of WIN55,212?2-induced amnestic-like effect was counteracted by the dopamine D2 receptor antagonist, sulpiride (0.25, 0.5 and 1 mg/kg/day * 3-days, S.C.), administered 30 min before each injection of apomorphine (0.5 mg/kg/day * 3-days, S.C.). The D1 receptor antagonist, SCH 23390 (0.01, 0.02, 0.07 and 0.1 mg/kg/day * 3-days, S.C.), was ineffective in this respect. The results suggest that subchronic apomorphine treatment may induce dopamine D2 receptor sensitization, which in turn prevented amnesia induced by WIN55, 212?2.
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